Local ethic review board approval was applied for and obtained before the study began. Patients with known Sjögren's syndrome were identified from clinical files and recruited for the study until a total of 10 subjects was enrolled (SS group). In a similar fashion, a group of 10 normal subjects also was recruited and enrolled. The normal subjects were matched to the subjects with Sjögren's syndrome by age and sex (normal group). All recruited subjects read and signed an information and consent form before participating in the study. All subjects were treated in accordance with the Declaration of Helsinki.
To reduce possible confounding effects, subjects with lacrimal plugs, evident punctal occlusion from other causes, or a history of contact lens wear were excluded from the study. Patients with previous eye surgery, including refractive surgery, or relevant ocular pathology (excepting SS) also were excluded. All subjects had a best corrected acuity of at least 1.0 (20/20).
Baseline measures of dry eye were taken for both groups, to confirm the diagnosis of dry eye in the SS group. These measures included tear breakup time (TBUT), the extent of rose bengal and fluorescein staining, and a subjective questionnaire—a Chinese translation of the Ocular Surface Disease Index (OSDI). The OSDI is a validated questionnaire for measuring the severity of dry eye disease.
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All subjects in both groups had baseline contrast sensitivity (CS) tested using the Functional Acuity Contrast Test (FACT), a contrast sensitivity test included in the OPTEC 6500 Contrast Sensitivity View-in Tester (Stereo Optical Company, Inc., Chicago, IL). After baseline testing in the SS group, a drop of Systane Ultra (Alcon Laboratories, Fort Worth, TX) was instilled in the eye and contrast sensitivity was retested at 5 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours after installation. The technician testing CS was masked as to which drop was instilled. Contrast sensitivity was measured at a number of different spatial frequencies, from 1.5 to 18 cycles/deg (cpd).
The SS group returned on 3 separate occasions after the initial visit, 7 days apart, which was considered sufficient for any required washout. On subsequent visits, the contrast sensitivity was tested before drop instillation, and 5 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours after instillation. The drops instilled each week were Systane Ultra (polyethylene glycol 400 0.4%, propylene glycol 0.3%, with HP Guar; Alcon Laboratories), ocular saline solution, Refresh Plus (carboxymethylcellulose sodium 0.5%; Allergan, Irvine, CA), and Hycosan (sodium hyaluronate 0.1%; Ursapharm, Arzneimittel GmbH, Saarbrücken, Germany), in that order. Given the washout period and the short time of the measurements, randomization was not considered necessary. To avoid subsequent use of brand names, they are referred to as SU, Saline, RP, and H in the remainder of this study.
Differences in baseline data from the first visit were compared between the normal and SS group using Student's t-test. Differences in baseline contrast sensitivity also were compared using an ANOVA with two factors (spatial frequency and group). Where overall statistically significant differences were reported, post hoc analysis was performed using Tukey's honestly significant difference (HSD) test.
The effects of the artificial tears on the contrast sensitivity of the SS group also were analyzed using appropriate techniques. Initial analysis was conducted using time as a repeated measures variable. In this way, random effects from the variability of contrast sensitivity between visits were eliminated; the repeated measures analysis was based on the change from the baseline recorded just before the artificial tears were instilled. Initial testing was performed using ANOVA. Statistically significant differences were investigated further using Tukey's HSD test, with measured differences from baseline being the critical effect.
Finally, for those times and frequencies where a significant increase in contrast sensitivity was noted, the average contrast sensitivity measure at that time and frequency was compared to the baseline contrast sensitivity in the normal group at the same frequency. This was a measure of whether the artificial tear provided the SS group subject with relatively normal contrast sensitivity. This was performed using a series of independent t-tests.
Statistical analyses were performed using the Statistica data analysis software system, Version 10 (StatSoft, Inc., Tulsa, OK). Parametric variables were tested using t-tests and ANOVAs with a significance set at P < 0.05.